ER stress and the unfolded protein response in neurodegeneration
Author
dc.contributor.author
Hetz Flores, Claudio
Author
dc.contributor.author
Saxena, Smita
Admission date
dc.date.accessioned
2018-06-18T17:11:25Z
Available date
dc.date.available
2018-06-18T17:11:25Z
Publication date
dc.date.issued
2017
Cita de ítem
dc.identifier.citation
Nature Reviews Neurology Vol. 13 (8): 477-491
es_ES
Identifier
dc.identifier.other
10.1038/nrneurol.2017.99
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/148969
Abstract
dc.description.abstract
The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation. ER stress triggers a signalling reaction known as the unfolded protein response (UPR), which induces adaptive programmes that improve protein folding and promote quality control mechanisms and degradative pathways or can activate apoptosis when damage is irreversible. In this Review, we discuss the latest advances in defining the functional contribution of ER stress to brain diseases, including novel evidence that relates the UPR to synaptic function, which has implications for cognition and memory. A complex concept is emerging wherein the consequences of ER stress can differ drastically depending on the disease context and the UPR signalling pathway that is altered. Strategies to target specific components of the UPR using small molecules and gene therapy are in development, and promise interesting avenues for future interventions to delay or stop neurodegeneration.
es_ES
Patrocinador
dc.description.sponsorship
FONDAP
15150012
US Office of Naval Research-Global (ONR-G)
N62909-16-1-2003
Millennium Institute
P09-015-F
FONDEF
ID16I10223
D11E1007
US Air Force Office of Scientific Research
FA9550-16-1-0384
CONICYT-Brazil
441921/2016-7
ALS Therapy Alliance
2014-F-059
Muscular Dystrophy Association
382453
Michael J Fox Foundation for Parkinson's Research - Target Validation
9277
FONDECYT
1140549
ALSRP Therapeutic Idea Award
AL150111
Synapsis Foundation
Stiftung UNISCIENTIA
Frick foundation for ALS research
Swiss National Science Foundation
European Research Council
725825